Posts tagged cortical neurons
Articles and news from the latest research reports.
Human Cortical Neurons with interconnecting dendrites, 4,200X by David Scharf.
Cortical Neurons make up the brain’s cortex which in part makes up the cerebral cortex, responsible for memory, attention, perceptual awareness, thought, language, and consciousness.
(Image Credit: BNPS/RPS/David Scharf)
Researchers Find Surprising Role of Critical Brain Protein
If the violins were taken away from the musicians performing Beethoven’s 9th symphony, the resulting composition would sound very different. If the violins were left on stage but the violinists were removed, the same mutant version of the symphony would be heard.
But what if it ended up sounding like “Hey Jude” instead?
This sort of surprise is what scientists from the Virginia Tech Carilion Research Institute had during what they assumed to be a routine experiment in neurodevelopment. Previous studies had shown that the glycoprotein Reelin is crucial to developing healthy neural networks. Logically, taking away the two receptors that Reelin is known to act on early in the brain’s development should create the same malformations as taking away Reelin itself.
It didn’t.
“We conducted the experiment thinking we’d see the same defects for both cases – Reelin deficiency and its receptors’ deletion – but we didn’t,” said Michael Fox, an associate professor at the research institute and the lead author of the study. “If you take away the receptors instead of the targeting molecule, you get an entirely separate set of abnormalities. The results raise the question of the identity of other molecules with which Reelin and the two receptors are interacting.”
The study, first published online in June in Neural Development, could prove useful for the development of therapies and diagnostics to combat brain disease.
In the early stages of neural development, neurons grow from the retina to a small portion of the brain called the thalamus. All sensory information coming into the brain gets routed through this region, before being transmitted to the cerebral cortex for further processing. Because these retinal neurons carry specific types of information, they must connect to specific places in the thalamus, which Reelin helps them find.
In the experiment, the scientists bred mice lacking both Reelin receptors known to be critical for neurons to navigate their targets during development. The scientists expected the neurons in the mutants to become lost and unable to find their targets, which is what happens in Reelin-deficient mice. Instead, the neurons were able to locate their targets, but those targets had wandered off.
While these results were surprising, they weren’t the most interesting of the experiment. Although most neurons look the same to people without advanced training in neuroscience, many different types are intermixed in distinct regions with strict borders. How these borders are formed, however, is still an open question.
“Many of us have questioned how you can have such a crisp boundary between two regions of the brain,” said Jianmin Su, a research assistant professor at the research institute and first author of the study. “I always thought it was a large number of cells creating some kind of cue or environment, but that isn’t what this experiment indicates.”
In the mice without the Reelin receptors, neurons from one part of the thalamus migrated to an area where they weren’t supposed to be. Even though only a handful of neurons were misplaced, they did not mingle with their new neighbors. They stayed separate.
“The result is a baffling curiosity that nobody in the lab expected – just how distinct these little regions can be,” Fox said. “How do just a few cells create such a barrier? How many cells does it take? Maybe these little islands can teach us something about how you create boundaries between larger regions of functionally similar cells.”
This experiment isn’t the only example Fox has had recently of neurons invading regions in which they weren’t supposed to be. In a second experiment, researchers examined how neurons from the cortex connect to the thalamus during the initial stages of development.
And neurons seem to be polite.
The results showed that neurons from the cortex grow to the edge of the part of the thalamus dedicated to visual signals, called the dorsal lateral geniculate nucleus, but then stop. In fact, they stay on standby for nearly two weeks before making their way into the region. It seems as though they’re waiting for the retinal neurons to make their connections before beginning to make their own. If researchers surgically removed the eyes or genetically removed the retinal cells connecting the eyes to the thalamus, neurons from the cortex invaded more than a week earlier than they were supposed to.
“It turns out that the cortical neurons are waiting for the retinal axons to mature and find the most appropriate spots to connect before they’re allowed to come in,” said Fox. “There’s some form of instructional role that retinal axons play in the timing of the cortical axons entering.”
(Source: newswise.com)
MIT study sheds light on what causes compulsive behavior, could improve OCD treatments.
By activating a brain circuit that controls compulsive behavior, MIT neuroscientists have shown that they can block a compulsive behavior in mice — a result that could help researchers develop new treatments for diseases such as obsessive-compulsive disorder (OCD) and Tourette’s syndrome.
About 1 percent of U.S. adults suffer from OCD, and patients usually receive antianxiety drugs or antidepressants, behavioral therapy, or a combination of therapy and medication. For those who do not respond to those treatments, a new alternative is deep brain stimulation, which delivers electrical impulses via a pacemaker implanted in the brain.
For this study, the MIT team used optogenetics to control neuron activity with light. This technique is not yet ready for use in human patients, but studies such as this one could help researchers identify brain activity patterns that signal the onset of compulsive behavior, allowing them to more precisely time the delivery of deep brain stimulation.
“You don’t have to stimulate all the time. You can do it in a very nuanced way,” says Ann Graybiel, an Institute Professor at MIT, a member of MIT’s McGovern Institute for Brain Research and the senior author of a Science paper describing the study.
The paper’s lead author is Eric Burguière, a former postdoc in Graybiel’s lab who is now at the Brain and Spine Institute in Paris. Other authors are Patricia Monteiro, a research affiliate at the McGovern Institute, and Guoping Feng, the James W. and Patricia T. Poitras Professor of Brain and Cognitive Sciences and a member of the McGovern Institute.
Controlling compulsion
In earlier studies, Graybiel has focused on how to break normal habits; in the current work, she turned to a mouse model developed by Feng to try to block a compulsive behavior. The model mice lack a particular gene, known as Sapap3, that codes for a protein found in the synapses of neurons in the striatum — a part of the brain related to addiction and repetitive behavioral problems, as well as normal functions such as decision-making, planning and response to reward.
For this study, the researchers trained mice whose Sapap3 gene was knocked out to groom compulsively at a specific time, allowing the researchers to try to interrupt the compulsion. To do this, they used a Pavlovian conditioning strategy in which a neutral event (a tone) is paired with a stimulus that provokes the desired behavior — in this case, a drop of water on the mouse’s nose, which triggers the mouse to groom. This strategy was based on therapeutic work with OCD patients, which uses this kind of conditioning.
After several hundred trials, both normal and knockout mice became conditioned to groom upon hearing the tone, which always occurred just over a second before the water drop fell. However, after a certain point their behaviors diverged: The normal mice began waiting until just before the water drop fell to begin grooming. This type of behavior is known as optimization, because it prevents the mice from wasting unnecessary effort.
This behavior optimization never appeared in the knockout mice, which continued to groom as soon as they heard the tone, suggesting that their ability to suppress compulsive behavior was impaired.
The researchers suspected that failed communication between the striatum, which is related to habits, and the neocortex, the seat of higher functions that can override simpler behaviors, might be to blame for the mice’s compulsive behavior. To test this idea, they used optogenetics, which allows them to control cell activity with light by engineering cells to express light-sensitive proteins.
When the researchers stimulated light-sensitive cortical cells that send messages to the striatum at the same time that the tone went off, the knockout mice stopped their compulsive grooming almost totally, yet they could still groom when the water drop came. The researchers suggest that this cure resulted from signals sent from the cortical neurons to a very small group of inhibitory neurons in the striatum, which silence the activity of neighboring striatal cells and cut off the compulsive behavior.
“Through the activation of this pathway, we could elicit behavior inhibition, which appears to be dysfunctional in our animals,” Burguière says.
The researchers also tested the optogenetic intervention in mice as they groomed in their cages, with no conditioning cues. During three-minute periods of light stimulation, the knockout mice groomed much less than they did without the stimulation.
Scott Rauch, president and psychiatrist-in-chief of McLean Hospital in Belmont, Mass., says the MIT study “opens the door to a universe of new possibilities by identifying a cellular and circuitry target for future interventions.”
“This represents a major leap forward, both in terms of delineating the brain basis of pathological compulsive behavior and in offering potential avenues for new treatment approaches,” adds Rauch, who was not involved in this study.
Graybiel and Burguière are now seeking markers of brain activity that could reveal when a compulsive behavior is about to start, to help guide the further development of deep brain stimulation treatments for OCD patients.